Update on the Role of T Cells in Cognitive Impairment

Abstract

The central nervous system (CNS) has long been considered an immune-privileged site, with minimal interaction between immune cells, particularly of the adaptive immune system. Previously, the presence of immune cells in this organ was primarily linked to events involving disruption of the blood-brain barrier (BBB) or inflammation. However, current research has shown that immune cells are found patrolling CNS under homeostatic conditions. Specifically, T cells of the adaptive immune system are able to cross the BBB and are associated with aging and cognitive impairment. In addition, T-cell infiltration has been observed in pathological conditions, where inflammation correlates with poor prognosis. Despite ongoing research, the role of this population in the aging brain under both physiological and pathological conditions is not yet fully understood. In this review, we provide an overview of the interactions between T cells and other immune and CNS parenchymal cells, and examine the molecular mechanisms by which these interactions may contribute to normal brain function and the scenarios in which disruption of these connections lead to cognitive impairment. A comprehensive understanding of the role of T cells in the aging brain and the underlying molecular pathways under normal conditions could pave the way for new research to better understand brain disorders.

From Alzheimer's disease to vascular dementia: Different roads leading to cognitive decline

“…Within the immune system, adaptive immunity is also involved, as addressed by Ruiz‐Fernández et al Specifically, the role of T cells and their interplay with other immune and CNS parenchymal cells in health and disease are discussed, with an emphasis on the scenarios, mainly related to neurodegeneration and ageing (AD, Parkinson's disease, multiple sclerosis, ischemic stroke, etc. ), in which disruption of these connections may lead to cognitive impairment (Ruiz‐Fernández et al, 2024). The potential for the pharmacological modulation of T cells is reviewed, starting from molecules that prevent lymphocyte infiltration in the CNS (monoclonal antibodies against integrins, like natalizumab, or against CD49d; S1P 1 receptor agonists such as fingolimod), with major clinical utility in multiple sclerosis, moving to modulators of the intestinal microbiota like sodium butyrate and valproic acid, with potential application in ischemic stroke, and the granulocyte‐macrophage colony‐stimulating factor sargramostim for AD.…”